Cloning and analysis of sodC, encoding the copper-zinc superoxide dismutase of Escherichia coli.

Benov and Fridovich recently reported the existence of a copper- and zinc-containing superoxide dismutase (CuZnSOD) in Escherichia coli (L. T. Benov and I. Fridovich, J. Biol. Chem. 269:25310-25314,1994). We have used the N-terminal protein sequence to isolate the gene encoding this enzyme. The gene, denoted sodC, is located at 37.1 min on the chromosome, adjacent to lhr and sodB. A monocistronic transcript of sodC accumulates only in stationary phase. The presence of a conventional leader sequence is consistent with physical data indicating that the E. coli enzyme, like other bacterial CuZnSODs, is secreted into the periplasm. Because superoxide cannot cross membranes, this localization indicates that the enzyme has evolved to defend periplasmic biomolecules against an extracytoplasmic superoxide source. Neither the source nor the target of the superoxide is known. Although once considered an exclusively eukaryotic enzyme, CuZnSOD has now been found in species that span three subdivisions of the purple bacteria. The bacterial CuZnSODs are more homologous to one another than to the eukaryotic enzymes, but active-site residues and structural motifs are clearly shared by both families of enzymes. The use of copper and an invariant disulfide bond suggest that the ancestral gene of present-day CuZnSODs evolved in an aerobic environment, long after the evolutionary split between the eukaryotes and the eubacteria. If so, a CuZnSOD gene must have been transferred laterally between members of these domains. The eukaryotic SODs most closely resemble that of Caulobacter crescentus, a relatively close descendant of the mitochondrial ancestor, suggesting that sodC may have entered the eukaryotes during the establishment of mitochondria.